Toll-like receptor 4 orchestrates the neutrophil recruitment into airways during the first steps of Bordetella pertussis infection

MORENO GRISELDA; ERREA AGUSTINA; LAURYE VAN MAELE; ROBERTS ROY; HÉLÈNE LÉGER; SIRARD JEAN CLAUDE; ARNDT BENECKE; RUMBO MARTÍN; HOZBOR DANIELA

MICROBES AND INFECTION

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2013 p. 708 - 718

1286-4579

The lipo-oligosaccharide (LOS) of Bordetella pertussis is a key modulator of the host immune response, mainly due to the role of its lipid A moiety in Toll-like receptor 4 (TLR4)-mediated signaling. Most of previous results on B. pertussis LOS were obtained when the bacteria had already been established within the host. Here, we found that this molecule participates in host-bacterial interaction as major determinant, very early in the course of bacterial infectious process. Within the first 2 hours of the infection, genes encoding the pro-inflammatory mediators TNF-alpha, IL-6, and IL-1 and the chemokines CXCL1, CXCL2 and CXCL5 known to participate in neutrophil-mediated mucosal defense were induced through TLR4 signaling. Moreover we observed that TLR4 signaling is absolutely needed to promote a rapid recruitment of neutrophils into the airways. Interestingly, the depletion of those neutrophils abolished the clearance of B. pertussis, thereby exacerbating lung infection. In summary, we determined that TLR4 is a central player in the orchestration of very early neutrophil-dependent innate defense against B. pertussis.